Développement et caractérisation d'une puce à cellules pour le criblage d'agents toxiques

COMPIEGNE-BU (601592101) / SudocSudocFranceF

Using digital to Foster strategic capability planning

Conférence UnleashInternational audienceTechnology is driving dramatic changes in companies. In the near future, 50% of work will be automated and most jobs that we see today will no longer exist. It is time the company's seriously rethinking its Corporate Strategic Workforce Planning process. Focusing on capabilities, not just the workforce, having a stronger outside-in approach, integrating trends, macro-economic data eased through digital solutions is a must to have. Regis will take a deep dive into how HR partnering, with Finance, Strategy, Technology, Business Intelligence can co-create a platform, a framework where leaders can reflect on their capabilities and needs five-ten years ahead and then identify trends and solutions

Evaluation of a liver microfluidic biochip to predict In vivo clearances of seven drugs in rats

We investigated metabolic clearances of phenacetin, midazolam, propranolol, paracetamol, tolbutamide, caffeine, and dextromethorphan by primary rat hepatocytes cultivated in microfluidic biochips. The levels of mRNA of the HNF4 alpha, PXR, AHR, CYP3A1, and CYP1A2 genes were enhanced in the biochip cultures when compared with postextraction levels. We measured a high and rapid adsorption on the biochip walls and inside the circuit for dextromethorphan and midazolam, a moderate adsorption for phenacetin and propranolol, and a low adsorption for caffeine, tolbutamide, and paracetamol. Drug biotransformations were demonstrated by the formations of specific metabolites such as paraxanthyne (caffeine), paracetamol (phenacetin), 1-OH midazolam (midazolam), paracetamol sulfate (paracetamol and phenacetin), and dextrorphan (dextromethorphan). We used a pharmacokinetic model to estimate the adsorption and in vitro intrinsic drug clearance values. We calculated in vitro intrinsic clearance values of 0.5, 3, 12.5, 83, 100, 160, and 900 mu L/min per 10(6) cells for the tolbutamide, caffeine, paracetamol, dextromethorphan, phenacetin, midazolam, and propranolol, respectively. A second model describing the liver as a well-stirred compartment predicted in vivo hepatic clearances of 0.1, 13.8, 30, 44.1, 61, 72, 85, and 61 mL/min per kg of body mass for the tolbutamide, caffeine, paracetamol, midazolam, dextromethorphan, phenacetin, and propranolol, respectively. These values appeared consistent with previously reported data

Asservissement et cophasage des antennes synthétiques dédiées à l'imagerie haute résolution pour l'astronomie

National audienc

Evaluation of seven drug metabolisms and clearances by cryopreserved human primary hepatocytes cultivated in microfluidic biochips

International audienceWe present characterization of the metabolic performance of human cryopreserved hepatocytes cultivated in a platform of parallelized microfluidic biochips. The RTqPCR analysis revealed that the mRNA levels of the cytochromes P450 (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4) were reduced after the adhesion period (when compared to the post-thawing step). The microfluidic perfusion played a part in stabilizing and partially recovering the levels of the HNF4a, PXR, OAPT2, CYP 1A2, 2B6, 2C19 and 3A4 mRNA on contrary to non-perfused cultures. Fluorescein diacetate staining and P-gp mRNA level illustrated the hepatocytes' polarity in the biochips. Drug metabolism was assessed using midazolam, tolbutamide, caffeine, omeprazole, dextromethorphan, acetaminophen and repaglinide as probes. Metabolite detection and quantification revealed that CYP1A2 (via the detection of paraxanthine), CYP3A4 (via 1-OH-midazolam, and omeprazole sulfone detection), CYP2C8 (via hydroxyl-repaglinide detection), CYP2C19 (via hydroxy-omeprazole detection) and CYP2D6 (via dextrorphan detection) were functional in our microfluidic configurations. Furthermore, the RTqPCR analysis showed that the drugs acted as inductors leading to overexpression of mRNA levels when compared to post-thawing values (such as for HNF4a, PXR and CYP3A4 by dextromethorpahn and omeprazole). Finally, intrinsic in vitro biochip clearances were extracted using a PBPK model for predictions. The biochip predictions were compared to literature in vitro data and in vivo situations

Spatial and Temporal Variability of Diffusive CO 2 and CH 4 Fluxes From the Amazonian Reservoir Petit‐Saut (French Guiana) Reveals the Importance of Allochthonous Inputs for Long‐Term C Emissions

International audienceVariability in greenhouse gas emissions from reservoirs creates uncertainty in global estimates of C emissions from reservoirs. This study examines the temporal and spatial variability in CO2 and CH4 surface water concentrations and diffusive fluxes from an Amazonian reservoir using an original data set combining both a high temporal (1 central site × 22 years) and spatial (44 sites × 1 season) resolution monitoring. The gas concentrations at the central site decreased over time and suggested reduced bioavailability of C in the initial flooded soil but exhibited strong seasonal variation. Not accounting for this variability may result in uncertainties in estimates of annual concentrations (ranging from −68.9% to +260% for CH4 and from −71.5% to +156% for CO2) and thus in estimates of diffusive gas emissions. Gas concentrations and diffusive fluxes exhibited high spatial variability in the reservoir, 24 years after impoundment. In particular, diffusive fluxes were higher in littoral and transitional areas than in open areas, suggesting a large contribution of allochthonous C to current gaseous emissions. Not accounting for this spatial variability in diffusive fluxes may underestimate the total emissions expressed in CO2 equivalents from the whole reservoir by 50.7%. Our study stresses the importance of well‐resolved temporal and spatial monitoring to provide reliable estimated of C emissions and a comprehensive understanding of the processes involved; both of these inputs are needed to support decision‐making for developing energy strategies